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  Regulation of Skeletal Muscle Stem Cell Quiescence by Suv4-20h1-Dependent Facultative Heterochromatin Formation

Boonsanay, V., Zhang, T., Georgieva, A., Kostin, S., Qi, H., Yuan, X., et al. (2016). Regulation of Skeletal Muscle Stem Cell Quiescence by Suv4-20h1-Dependent Facultative Heterochromatin Formation. CELL STEM CELL, 18(2), 229-242. doi:10.1016/j.stem.2015.11.002.

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 Creators:
Boonsanay, Verawan1, Author              
Zhang, Ting2, Author              
Georgieva, Angelina1, Author              
Kostin, Sawa3, Author              
Qi, Hui1, Author              
Yuan, Xuejun1, Author              
Zhou, Yonggang2, Author              
Braun, Thomas1, Author              
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              
2Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              
3Electron Microscopy, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591707              

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Free keywords: SATELLITE CELLS; SELF-RENEWAL; MUSCULAR-DYSTROPHY; CHROMATIN; REGENERATION; MYOD; MOUSE; MICE; EZH2; INACTIVATIONCell Biology;
 Abstract: Skeletal muscle stem cells (MuSCs) are required for regeneration of adult muscle following injury, a response that demands activation of mainly quiescent MuSCs. Despite the need for dynamic regulation of MuSC quiescence, relatively little is known about the determinants of this property. Here, we show that Suv4-20h1, an H4K20 dimethyltransferase, controls MuSC quiescence by promoting formation of facultative heterochromatin (fHC). Deletion of Suv4-20h1 reduces fHC and induces transcriptional activation and repositioning of the MyoD locus away from the heterochromatic nuclear periphery. These effects promote MuSC activation, resulting in stem cell depletion and impaired long-term muscle regeneration. Genetic reduction of MyoD expression rescues fHC formation and lost MuSC quiescence, restoring muscle regeneration capacity in Suv4-20h1 mutants. Together, these findings reveal that Suv4-20h1 actively regulates MuSC quiescence via fHC formation and control of the MyoD locus, thereby guarding and preserving the stem cell pool over a lifetime.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: CELL STEM CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 18 (2) Sequence Number: - Start / End Page: 229 - 242 Identifier: ISSN: 1934-5909